The objective of this study is to examine membrane protein patterns of human leukemias and lymphomas in SDS polyacrylamide electrophoresis gels in order to identify subsets of these malignancies and to compare these tumor protein patterns to normal subsets of lymphocytes in resting states and after mitogenic and alloantigenic activation. These latter experiments can reveal whether tumors represent expansions of normal lymphocyte subpopulations at some physiological state. (35S)methionine internal labeling of lymphoblasts and SDS slab gel electrophoresis and autoradiography of their isolated membranes has demonstrated more than 100 proteins with variable patterns among cell lines. Subset-specific proteins have been identified: p110 on T cells, p65 on only CEM, p85 and p29,34 (HLA-DR) on B lymphoblasts. Dramatic day-to-day changes in membrane proteins of normal T lymphocytes as a function of mitogenic activation have been found. These studies will be expanded in order to define band patterns which are specific to subsets of lymphoid tumors, to identify subset-specific molecules which can be isolated for the preparation of diagnostic antisera, to evaluate whether tumor cells are "frozen" at some differentiation step or experience protein band pattern changes in tissue culture or upon stimulation with mitogens or with MLR culture supernatant factors. Diagnosis of subsets of acute lymphoblastic leukemia, chronic lymphocytic leukemia and non-Hodgkin's lymphomas will be emphasized by comparison of membrane protein "fingerprint" patterns in electrophoresis gels with the clinical course of each patient.